Lung cancer is the leading cause of cancer-related mortality in both men and women. An estimated 159,480 deaths have occurred in the U.S. in 2013, accounting for about 27% of all cancer deaths. Lung cancer can be histopathologically classified as small cell (15%) or non-small cell (84%) for the purposes of treatment, with the latter consisting of large cell carcinoma (LCC), adenocarcinoma and squamous cell carcinoma (SCC). Although surgery, radiotherapy, chemotherapy, and even EGER targeted therapies such as cetuximab (Erbitux), erlotinib (Tarceva), and gefitinib (Iressa) have been used to treat different stages or types of lung cancer, the 5-year survival rates for small cell carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) remain low, at 6% and 18%, respectively.
One major cause for this disappointing outcome is lack of selectivity for conventional chemotherapeutics in cancer treatment, which results in a narrow therapeutic window and severe damage to normal tissues. The other reason is high interstitial fluid pressure (IFP) of solid tumors which makes it difficult for anticancer agents or even small molecular tyrosine kinase inhibitors commonly used in targeted therapy to enter into the tumor site. It has been shown that the amount of drug accumulated in normal viscera is ˜10- to 20-fold higher than that in the same weight of tumor site, and that many anticancer drugs are not able to penetrate more than 40-50 μm (equivalent to the combined diameter of 3-5 cells) from the vasculature. These deficiencies often lead to limited therapeutic function and multiple drug resistance, thereby compromising clinical prognosis.